Bone marrow contains mesenchymal progenitor cells that we have called mesenchymal stem cells (MSCs). The MSCs have been shown to have the capacity to differentiate into a variety of unique mesenchyrnal tissues including bone, cartilage, muscle, fat, tendon, marrow stroma, and other connective tissues. Osteogenesis Imperfecta (OI) is a disease that is caused by mutations in the type I collagen gene. One of the progeny of MSCs, the osteoblast, is responsible for fabricating bone and, thus, a mutation in the type I collagen gene can result in bone with physical and mechanical properties that are compromised depending on the exact location and extent of the mutation. One possible curative therapy for OI is to transplant and optimize the engraftment of allogenic MSCs whose type I collagen genes are normal. As a first step to develop a procedure for effectively delivering genetically normal progenitor cells to bone for a variety of NEW therapeutic purposes, including OI, a new cell targeting strategy has been developed. The progenitor cells are modified by non-genetic insertion of macromolecules containing tissue addresses that transiently occupy positions on the outer most surface of the cell. The addition of these addressing macromolecules has been called CELL PAINTING. A newly developed, simple Cell Painting technology involves coating cells with palmitated Protein-A and then exposing these cells to a fusion protein containing the Protein A-binding FC portion of antibodies and a tissue targeting peptide. These tissue targeting peptide address assemblies are removed from the cell surface by normal mechanisms of membrane turnover within 48 to 72 hours and are thus, harmless in a long-term sense. The Objective of the research proposed here is to optimize the Cell Painting technology and to identify the most effective bone- or bone-marrow-specific addressing peptides to optimize engraftment. The HYPOTHESIS that we will focus our experimentation on is that marrow derived mesenchyrnal progenitor cells delivered back to the marrow in a specific and effective manner will engraft in sufficient numbers to effect the bone physiology of the hosts and provide a curative therapy for OI.